Many lines of evidence have implicated the prefrontal cortex and the medial dorsal nucleus of the thalamus (MD) in schizophrenia (for review see 39,40,41,42). Our laboratory in particular has shown a decrease in MAP2, a protein found in dendrites and cell bodies as well as a decrease in the number of primary and secondary dendrites in areas 9 and 32 of the prefrontal cortex (5,14). Additionally, in collaboration with Dr. William Byne we have shown a decrease in the volume of the MD and cell loss in the different subdivisions of the MD (26). These data are important for several reasons most importantly is that the MD projects to the affected areas in the prefrontal cortex (33,34,35,36) and that cellular development in the prefrontal cortex is in part dependent upon the thalamic inputs to the cortex (37). We hypothesis that the cell loss in the MD may be responsible for the alterations in the prefrontal cortex. To test this we will lesion the MD of P4 rat pups and let them age to P14 and P28 and then examine the expression of MAP2, the morphology of the pyramidal cells and the expression of two calcium binding proteins, parvalbumin and calbindin, to examine alterations in GABAergic cells. We will use stereologic methods to count the number of primary and secondary basilar dendrites of pyramidal cells in layers III and V as well as the number of immunoposifive parvalbumin and calbindin cells. Additionally, we will use area fraction analysis to measure the amount of staining observed for MAP2 as well as parvalbumin and calbindin. We will compare the results obtained to those observed in schizophrenia to determine if a lesion of the MD, therefore, a loss of cells in the MD, plays a role in the etiology of schizophrenia. The proposed research is a first attempt to try to understand the etiology of schizophrenia by examining if a developmental lesion of the MD affects the development of cortical regions such as the prefrontal cortex.